Non-myeloablative autologous hematopoietic stem cell transplantation for systemic lupus erythematosus

Abstract

Patients with systemic lupus erythematosus (SLE) usually respond well to immunosuppressive medications. However, there is a subset of refractory SLE patients for whom current strategies are insufficient to control disease. Here we report results of autologous non-myeloablative hematopoietic stem cell transplantation (HSCT) single arm trial performed at Northwestern University Feinberg School of Medicine between February 1997 and January 2005 which involved 50 patients with SLE refractory to standard immune suppressive therapies and either organ- or life-threatening visceral involvement. The primary endpoint was survival, both overall survival and disease free survival. Secondary endpoints include systemic lupus erythematosus disease activity index (SLEDAI), serology (ANA and anti-ds DNA), complement (C3 and C4), and changes in renal and pulmonary organ function assessed pre-treatment and at 6, 12 months and then yearly for 5 years. Peripheral blood stem cells were mobilized with intravenous (IV) cyclophosphamide (CY) (2.0 g/m2) and subcutaneous G-CSF (5 μg/kg/day). The graft was enriched ex vivo by CD34+ immunoselection. Conditioning regimen consisted of IV CY (200 mg/kg) and equine anti-thymocyte globulin (90 mg/kg). Fifty patients were enrolled and underwent stem cell mobilization. Two patients died after mobilization, one from disseminated mucormycosis and another from active lupus after postponing the transplant for 4 months. Forty-eight patients underwent lupus non-myeloablative HSCT with no treatment related mortality. By intention to treat, treatment related mortality was 2% (1/50). With a mean follow-up of 29 months (range 6 month to 7.5 years), overall survival was 84%, and probability of disease free survival at 5 years post transplant was 50%. SLEDAI, ANA, anti-ds DNA, complement, and lung diffusion capacity of carbon monoxide adjusted for hemoglobin (DLCOadj) significantly statistically (P ≤ .05) improved. Renal function assessed by creatinine and creatinine clearance remained stable overall. Results of our trial suggest that in patients with treatment refractory SLE autologous non-myeloablative HSCT markedly ameliorates disease activity and so confers long term disease remission, improvement in serologic markers, and either stabilization or reversal of organ dysfunction.